Hypertension is one of the commonest cardiovascular diseases. The main manifestation of its clinical syndrome is elevation of arterial blood pressure in systemic circulation. The two main types of hypertension are primary and secondary hypertension. The majority is primary hypertension. More than 95 percent of hypertensive patients suffer from it. As the development of social economy, improvement of life level of the people, and the prolongation of lifetime of human, the prevalence of hypertension shows a trend of continuously elevation. As estimated, 18.8 percent of adults in China suffer from hypertension, and there are 0.16 billion hypertensive patients in the whole country. In this population of hypertensive patients, awareness rate of hypertension is 30.2 percent, treatment rate is 24.7 percent, and control rate is 6.1 percent, which are all in worse level.
If hypertension is not controlled and treated effectively, it will cause coronary arteriosclerosis, coronary heart disease, angina pectoris, and even very serious complication, such as hypertensive heart disease and heart failure. In addition, long-term hypertension will result in renal dysfunction, which makes patients incapacitated, even losing their lives. The recently published result of eight-year follow-up survey of 170 thousand people in China, all over 40 years old, showed that cardiovascular disease is already the first cause of death in China, and hypertension is one of the major risk factors. The burden brought from hypertension and its related diseases is so heavy. An estimation of 300 billion RMB is expensed by cardiovascular diseases each year in China.
Drug treatment is one of the major therapies to control hypertension effectively. In the therapeutic field of antihypertensive drugs, common antihypertensive drugs include the types as follows: 1) diuretics, which act by increasing the excretion by the kidneys of sodium in the urine to aid the elimination of sodium and water from the body, and lower blood pressure by reducing blood volume. As a basic agent, diuretics are used to treat mild and moderate hypertension, especially suitable for aged or hypertensive patients combined with heart failure. The main side effects associated with diuretics is an increased elimination of potassium, resulting in a low level of potassium in the body, which increases the risk of heart rhythm disturbances that can be serious, and also hinders antihypertensive effect of diuretics. 2) β receptor blockers, which produce antihypertensive effects by many kinds of action pathways, including several aspects as follows: (1)reduction in cardiac output to make the body produce adaptive response, thus reduces the peripheral vascular resistance and lowers the blood pressure; (2) blockade of β receptor in central nervous system to decrease neural conduction of sympathetic fibers; (3) blockade of the excitatory receptor of presynaptic membrane β2 to decrease the release of NE; (4) inhibition of the release of renin; (5) increasing the vasodilative effect of ANP and PGI2;  (6) rebuilding pressure receptor and so on. The adverse effects of β receptor blockers include the following: fatigue, limb cold, gut discomfort, eye scintillation, blind spot and so on. 3) α1 receptor blockers, which dilate resistance vessels and capacitance vessels by selective action on the synaptic α1 receptor and thus decrease arterial blood pressure. α1 receptor blockers have significant antihypertensive effect, which also can decrease plasma cholesterol and triglyceride concentration, improve insulin resistance, and slightly reverse LVH. With inhibitive effect on prostate, they can significantly improve dysuria for the patients of prostatic hyperplasia. α1 receptor blockers are applicable for the patients with glucose or lipid metabolic abnormality or prostatic hyperplasia. The adverse effects of these agents are headache, dizziness, palpitation, asthenia and so on. Their disadvantages are the appearance of peripheral edema, weight gain, and the first dose phenomenon i.e., postural hypotension. 4) Ca++ antagonists, which selectively block the influx of Ca++ in the specific L type calcium channel on the membrane of vascular smooth muscle and myocardium to relax vascular smooth muscle and reduce the vascular resistance. The main adverse effects of Ca++ antagonists are flush face (particularly seen in short-effect dihydropyridines), headache, dizziness, palpitation, constipation and ankle edema, which are related to vascular excessive vasodilatation. The adverse effects can be alleviated by using small dosage at the beginning. 5) ACE inhibitors, which act on renin-angiotensin-aldosterone system (RAS). These agents bind with Angiotensin I converting enzyme to inhibit Angiotensin II formation, and make the decomposition of bradykinin slow, which result in vasodilatation and decline of blood pressure. The common main adverse effects of ACEI are dry cough and angioneurotic edema. If replenishers with potassium together with diuretics retaining potassium are taken simultaneously, hyperkalemia will easily appear.
Angiotensin II receptor blacker (ARB) is a new type of antihypertensive agents acting on renin-angiotensin-aldosterone system (RAS) after ACEI. ABR acts on the terminal position of RAS, which can play highly efficient role to block the binding of Angiotensin II (Ang II) with its receptor, so that achieve the functions of dilating blood vessels and reducing blood pressure. In 1994, the first (AT1) antagonist, losartan potassium was marketed by Merck Company (US). Because of its good efficacy, many pharmaceutical companies all over the world devoted into this field. The same type of products such as valsartan (Novartis), irbesartan (Sanofi Aventis), candesartan (Takeda), eprosartan (Smiklane Beecham), telmisartan (Boehringer Ingelheim), olmesartan (Sankyo), were marketed subsequently. The antihypertensive efficacy of sartan-class drugs is similar to ACEI and Ca++ antagonists. However, ARB-class drugs have more tolerance, fewer side effects and fewer common adverse effects such as causing cough and edema, so that are safer drugs to treat hypertension. As the tangible efficacy from the special mechanism of ARB-class drugs, they have become the mainstream drugs in antihypertensive market.
Nevertheless, the antihypertensive treatment is long-term, even life-long, which need to have the characteristics of low toxicity and protection of vital target organs, as well as tangible efficacy. The antihypertensive drugs mentioned above do not meet the above requirement. Therefore, there is an urgent need to continually develop novel antihypertensive drugs with high efficiency, low toxicity and the function of protecting vital target organs.